The use of Neutron Capture Therapy (NCT) for treatment of cancer or tumors is well known by those skilled in the art. NCT operates as a several step process. First, a reagent having a high cross section for neutron capture is selected. Presently, the use of gadolinium and boron as reagents is preferred by those skilled in the art. The reagent must then be combined with a pharmaceutical compound which is selectively absorbed by tumor cells. The combined pharmaceutical compound and reagent are administered to the patient, whereupon the reagent is selectively absorbed by tumor cells. Several compounds containing suitable reagents which are selectively absorbed by tumor cells are known in the art, including, but not limited to, borane sodium borocaptate, boronophenylalanine, boronated monoclonal antibodies, and gadolinium contrast agents. Next, neutrons are directed towards the tumor site. By virtue of the large cross section for neutron capture exhibited by the reagent as compared with the cross section of other elements found in surrounding tissue, the reagent will preferentially capture neutrons to the exclusion of the surrounding tissue. Upon exposure to neutrons, tissue containing reagent absorbs or captures neutrons and the reagent decays. Upon neutron capture, decay of the reagent releases high intensity, non-penetrating energy which destroys the cell immediately surrounding the reagent. Since the reagent is preferentially absorbed by tumor cells, the tumor cells are thereby likewise preferentially destroyed during the decay of the reagent to the exclusion of damage to the surrounding healthy tissue.
The use of NCT as an effective therapy for treating tumors has suffered from drawbacks associated with the introduction of neutrons to the tumor site. Most problematic is the introduction of neutrons to tumors buried beneath or covered by healthy and critical tissue. For example, those skilled in the art have recognized a need for a method for introducing neutrons to tumors located deep in critical tissue inside a patient, such as the patient's brain, without damage to the surrounding tissue. This need may be attributed to the characteristics of the neutrons themselves, and the effects of neutron bombardment on healthy tissue.
Neutrons may be classified according to the energy they exhibit. High energy neutrons, or fast neutrons, are typically recognized as neutrons emanating from unmoderated sources and having energies greater than about 0.5 MeV. Fast neutrons may be readily generated by methods well known in the art, and then administered to a patient. Fast neutrons penetrate tissue well, thus they can easily penetrate to reach tumors deeply imbedded in otherwise healthy tissue. However, fast neutrons suffer from a variety of drawbacks preventing their effective use in NCT. Fast neutrons cannot be aimed effectively using neutron focusing lenses, as the energy in fast neutrons is sufficient to cause the neutrons to escape the refraction of the interior walls of the lenses. Thus, when administered to a patient, fast neutrons cannot be directed exclusively to the tumor site. Also, fast neutrons scatter upon collisions with hydrogenated molecules typical of tissue and deposit excessive energy during those collisions within healthy cells surrounding the tumor site, which may damage the cells. The effects of (a) the inability to focus fast neutrons with neutron focusing lenses and (b) the scattering of the neutrons, insures that exposure of tissue to fast neutrons is not limited to the tumor site, and that healthy tissue surrounding the tumor site will therefore be damaged.
Intermediate energy neutrons, or epithermal neutrons, are partially moderated and are typically recognized as neutrons with energy ranging from about 0.2 eV to about 10 keV. Epithermal neutrons also exhibit sufficient energy to penetrate tissue to depths sufficient to reach deep tumors. Because of their lower energy, epithermal neutrons are in many ways superior to fast neutrons when used in NCT. Specifically, epithermal neutrons are of low enough energy that during collisions with healthy cells, insufficient energy is deposited in the healthy cells to cause damage. However, procedures and techniques known in the art for generating epithermal neutrons are expensive, and it is difficult to attain a consistent energy level among the generated epithermal neutrons. Also, epithermal neutrons exhibit the scattering observed in fast neutrons, which causes irradiation of healthy tissue surrounding the tumor.
Thermal and cold neutrons exhibit energy below that of epithermal neutrons. Fast neutrons are readily converted, or moderated, to thermal neutrons by directing them through hydrogenous materials at about room temperature. Thermal neutrons are generally recognized as completely moderated neutrons having an average energy of about 0.025 eV. By cooling the hydrogenous moderator below room temperature, cold neutrons having energy below about 0.025 eV are produced. The collisions of the fast neutrons with hydrogen nuclei dissipates the kinetic energy, thus thermalizing the neutrons. In general, a reduction in energy in the neutrons improves the ability of a reagent to capture the neutrons. Thus, both thermal and cold neutrons (hereafter both thermal and cold neutrons being jointly referred to as cold so that the term "cold" as used hereinafter refers to neutrons having energies less than about 0.025 eV) are rapidly captured by suitable reagents having high cross sections for neutron capture. However, the loss of energy renders cold neutrons unable to penetrate tissue to a depth sufficient to allow capture by reagents absorbed in tumors deep with tissue.
Previously, limitations in the ability to control the trajectory of cold neutrons limited the effective use of cold neutrons in treating tumor sites because cold neutrons could not be directed exclusively at a tumor site and surrounding tissue would invariably be exposed to neutron attack. NCT thus resulted in the irradiation of not only tumors, but the surrounding tissue with cold neutrons. However, recent advances in capillary neutron optics have allowed great increases in the precision with which neutrons may be delivered to a given location, such as a tumor. Neutron focusing lenses, consisting of bundles of hollow capillaries, have been developed which allow thermal neutrons to be focused. By focusing cold neutrons towards a tumor site treated with a reagent having a high cross section for neutron capture, the tumor may be treated with minimal neutron attack on the surrounding tissue. Still, the advances in NCT enabled by neutron focusing lenses have not completely resolved the limitations of using cold neutrons in NCT for deep tumors because cold neutrons still lack sufficient penetration to reach deep tumors. Thus, those skilled in the art recognize a need for a method for providing cold neutrons to a deep tumor site without damaging the surrounding tissue.